60 e-Letters

published between 2020 and 2023

  • The ME community support NICE and reject the misguided attack in ‘Anomalies in the review process and interpretation of the evidence in the NICE guideline for chronic fatigue syndrome and myalgic encephalomyelitis

    The authors revised this Rapid Response at BMJ's request in line with BMJ's Terms and Conditions for Rapid Responses.

    Dear Editor,
    In the article ‘Anomalies in the review process and interpretation of the evidence in the NICE guideline for chronic fatigue syndrome and myalgic encephalomyelitis’ published in the Journal of Neurology, Neurosurgery & Psychiatry on 10th July 2023, the authors claim NICE invented a new definition of ME. These claims are unfounded as NICE used the Institute of Medicine (IOM) criteria which is now 8 years old and was created using a more robust process than many other definitions as it drew on samples from different countries and compared the most widely used definitions of ME.
    One area where NICE felt there was a gap in the IOM criteria was the lack of an empirical process alongside other methods. Leonard Jason's four-item empiric criteria were the only criteria that used adequate empiric methods, and this aligned very closely with the IOM criteria. As a result, NICE operationalised the IOM criteria for use in the NHS, with the four-item criteria helping to substantiate their approach.
    NICE does not measure a trial’s success based on the researchers’ own terms but by analysing the raw data and applying the committee's agreed protocol. This allows NICE to measure whether a treatment had an effect or not. This is striking when looking at the assertion that research showed that the favoured treatment...

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  • The association between childbirth delivery mode and development of multiple sclerosis

    Dear Editor,
    I am writing to express my appreciation for the enlightening article titled "Childbirth Delivery Mode and the Risk of Multiple Sclerosis: A Prospective Population-Based Study" [1] recently published in your esteemed journal. The study, which examines the potential relationship between childbirth mode and the subsequent risk of multiple sclerosis (MS) development, presents a comprehensive analysis and incites intriguing discussions. The authors embarked on a commendable endeavor by conducting a meticulous prospective cohort study encompassing individuals born in Norway between 1967 and 2003. Their investigation aimed to unravel the potential influence of caesarean section (CS) births on the risk of adult-onset MS. The findings unveil an association suggesting an 18% elevated risk of MS among individuals born via CS, as compared to those born vaginally, after considering an array of confounding factors. However, the authors astutely highlight that this association does not persist when a sibling-matched analysis is undertaken. Furthermore, this intriguing connection appears to be primarily confined to individuals born preterm or via emergency CS. Such nuanced insights underline the complexities underlying the childbirth mode and MS risk paradigm, necessitating a thoughtful interpretation of the findings.
    The authors acknowledge the divergent findings from previous studies, emphasizing the discrepancies between their results and those report...

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  • Correspondence on "Prognostic value of spinal cord lesion measures in early relapsing-remitting multiple sclerosis"

    I recently had the opportunity to read your article titled "Prognostic Value of Spinal Cord Lesion Measures in Early Relapsing-Remitting Multiple Sclerosis" [1] and I want to extend my appreciation for the significant contribution your research has made to the field of multiple sclerosis (MS). Your study investigated the relation of whole spinal cord lesion number (SCLN) and volume (SCLV) to the future occurrence and type of confirmed disability accumulation (CDA) in patients with relapsing-remitting MS. The manual delineation of SC lesions and the subsequent analyses provided valuable insights into the prospective value of these measures in predicting clinical outcomes. The significant association between the absence of SC lesions and reduced CDA risk suggests the importance of SC lesions as a prognostic indicator in MS. Additionally, the close correlation between SCLN and SCLV, and their independent association with CDA, provide further support for the relevance of these measures in predicting disability accumulation.
    The classification of CDA events into progression independent of relapse activity (PIRA) and relapse-associated worsening (RAW) facilitated a nuanced analysis of their association with SC lesion measures. The significant association with PIRA, but not RAW, hints at distinct underlying mechanisms for different types of disability progression, which could have implications for treatment strategies.
    While your study provides valuable insi...

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  • Shortcomings in the commentary by White et al.

    There are several shortcomings in the commentary by White et al. For brevity, this response focuses on four main points.

    1. New case definition
    In the past 20 years, multiple case definitions have been published that require post-exertional malaise (PEM) as a core feature of ME/CFS, such as the Canadian Consensus Criteria (CCC), International Consensus Criteria (ICC), and the Institute of Medicine (IOM) criteria. NICE’s definition is based on the latter.

    These case definitions are the ones used in research and clinical practice today. White et al. refer to the 1994 criteria developed by the Centers for Disease Control and Prevention (CDC) but the CDC no longer seems to use this case definition. Instead, they advise healthcare providers to diagnose ME/CFS using the IOM criteria where PEM is a required symptom.

    NICE evaluated scientific evidence for ME/CFS as it is currently defined and not for a case definition that was published nearly 30 years ago. Other reviews on ME/CFS, such as the recent one by IQWIG in Germany, have used a similar approach. (1)

    It is incorrect to state that NICE “downgraded nearly thirty years of research.” The previous NICE guidance from 2007 on ME/CFS already highlighted PEM as a core feature of ME/CFS, and studies that used this description were not downgraded in the evidence review. Neither were studies that used the CCC, ICC, or IOM criteria mentioned above.

    2. Blinding and subjective outcomes

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  • RE: CSF ferritin in the clinicopathological progression of Alzheimer's disease and associations with APOE and inflammation biomarkers

    Ayton et al. reported the association between ferritin, apolipoprotein E (APOE) and dementia-related biomarkers such as amyloid β42/total-tau and phosphorylated tau181 (p-tau181) in cerebrospinal fluid (CSF) (1). CSF ferritin and APOE were positively associated with p-tau181, which was most predominant in subjects without increase in amyloid β42/total-tau. I present information about the study.

    Pan et al. investigated the associations of CSF ferritin and CSF biomarkers of Alzheimer's disease (AD) (2). They found that CSF ferritin increased in subjects with more advanced categories of CSF biomarkers such as amyloid β42 and p-pau, although there were stronger relationships of CSF ferritin with p-tau and t-tau, rather than amyloid β42. This means that biological action of ferritin in the brain for AD may be more closely related to tau protein.

    Baringer et al. described brain iron homeostasis in Alzheimer's disease, Parkinson's disease, and other neurodegenerative diseases (3). They emphasized that endothelial cells of the blood-brain barrier were the site of iron transport regulation, and iron uptake, transcytosis, and release were mainly conducted. By controlling the excess of brain iron, neurodegenerative disorders may be improved. The mechanism that tau protein spreads through functionally connected neurons in Alzheimer's disease have been precisely reported (4), and it may be related to the excess of brain iron storage.


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  • Feminism demands radical revision to functional neurological disorder

    In “Functional neurological disorder is a feminist issue” by McLoughlin et al.,[1] authors explain that FND patients “suffer subtle and overt forms of discrimination”, suggesting that “FND clinical services and research are chronically underfunded in line with the neglect of disorders disproportionately affecting women”. Ultimately, they insist that feminists should support “parity of esteem” for FND with other neurological conditions.

    I suggest that the idea of an alliance between feminism and FND is highly problematic. First, authors minimize the seriousness of human rights violations against women in the name of hysteria. Second, they fail to consider the role that FND plays in healthcare gender bias across specialties. Third, they perpetuate the myth that functional diagnosis rarely errs, further threatening women’s safety in the healthcare system.

    First, while authors do acknowledge “objectification and exploitation” of women diagnosed with hysteria, their concern is merely that “some sociologists and scientists have opined that the diagnosis was used as a ‘patriarchal tool’ to silence or ignore complaints of women”. There’s no mention of sexualization of women’s symptoms in the name of hysteria, even as recently as ICD-10, or the range of sexual treatments to which “hysterical” women have been subjected, including genital mutilation. There’s no acknowledgment that these treatments, like sectioning based on the wishes of husbands, fathers, or sons, are...

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  • Epidural blood patch for spontaneous intracranial hypotension: Comments to the published guideline

    Dear Editor-in-Chief,
    We read with great interest the consensus guidelines for diagnosis and management of spontaneous intracranial hypotension (SIH). [1] In the absence of any recommendations, this guideline will help clinicians in formulating their diagnostic and management approaches for SIH. In this letter, we wish to discuss about the epidural blood patch (EBP) in the management of SIH. The role of targeted EBP for management of SIH has not been compared with non-targeted EBP in randomized controlled trials to establish superiority of one over the other. A recent systematic review of studies with 10 or more patients with SIH reported similar success with either technique. [2] However, where expertise is available and when the precise site of cerebrospinal fluid (CSF) leak is identifiable, it is prudent to consider targeted EBP as the first choice. This reduces the volume of autologous blood required, minimizes the need of reliance on gravity for spread of epidurally placed blood to the potential site of leak and decreases the procedure failure rates and need for subsequent EBPs or surgical interventions. In our center, which is a tertiary care neurosciences academic hospital, after an initial conservative management for a week, a targeted EBP is performed as the preferred approach to manage SIH. [3] If the site of leak is not determinable and if the expertise to perform cervical or thoracic EBP is not available, a non-targeted EBP may be the preferred interventi...

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  • RE: Insufficient sleep during adolescence and risk of multiple sclerosis: results from a Swedish case-control study

    Åkerstedt et al. conducted a case-control study with 2075 cases and 3164 controls to investigate the association between sleep and risk of multiple sclerosis (MS) (1). Sleep duration, circadian disruption and sleep quality during adolescence were used for sleep variables. The authors calculated the adjusted OR with 95% CIs using logistic regression models, and short sleep (<7 hours/night) and low sleep quality were significantly associated with increased risk of developing MS. I have a question regarding the ways of multivariate analysis.

    The ratio in the number of cases and controls is about 1.5 in this study. If the authors selected unconditional logistic regression analysis, OR might become conservative. If the authors selected conditional logistic regression analysis, the increased number of controls is preferable to make stable estimation. Instead of selecting a case-control study with a matching procedure, using all pooled data without a matching procedure can be selected for the analysis (2).

    Anyway, a recall method has a possibility of including bias and risk assessment of MS with subjective sleep variables should be paid with caution.

    1. Åkerstedt T, Olsson T, Alfredsson L, et al. Insufficient sleep during adolescence and risk of multiple sclerosis: results from a Swedish case-control study. J Neurol Neurosurg Psychiatry 2023;94(5):331-6.
    2. Hamajima N, Hirose K, Inoue M, et al. Case-control studies: matched controls...

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  • Usefulness of Retinal Imaging for Predicting Cognitive Impairment in Parkinson's Disease: Insights for Clinical Practice and Research

    We are writing to respectfully offer some additional comments on the recent publication of Hannaway et al. in JNNP titled “Visual dysfunction is a better predictor than retinal thickness for dementia in Parkinson’s disease”.

    While the authors provided interesting insights on the predictive value of higher order visual functions for dementia, we noticed that the authors did not find significant associations between parafoveal GCIPL (pfGCIPL) and cognition in their work, whereas our research did. As they mentioned, the range of cognitive impairment was higher in our sample, and possibly this might have driven our findings. However, we would like to add that the relationship between the retina and cognition is not linear, according to our data. As such, we calculated relative risks by categorizing continuous variables, which allowed us to identify non-linear relationships between pfGCIPL and cognitive impairment. Furthermore, we speculate that these variables do not exhibit a synchronous pattern of change over time, suggesting that the temporal trends are not closely linked, which might justify the lack of association in the current work.

    We do agree with the authors in that visual function is a good predictor of cognitive deterioration. Our previous work also demonstrated this fact, but we would like to highlight the benefits of retinal OCT imaging in this context, if its utility is validated. Retinal OCT imaging is a faster and easier-to-measure technique com...

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  • Functional neurological disorder - Gender, care and cost

    Functional neurological disorder is an important aspect with respect to burden and cost of management irrespective of gender as the authors have pointed out very rightly1.
    It can be chronic but most of the times present as an emergency therby increasing panic, inpatient admissions. Smooth care, workup and appropriate guidelines for the same may help a lot in such conditions.
    There is limited information, awareness, health care utilities, and economic burden of such patients which makes the situation more grim.
    So there should be multidisciplinary approach i.e. physiotherapy, occupational therapy, speech and language therapy, and psychological assessment. Functional neurological disorders overlap with refractory neurological conditions i.e. headache, seizure, focal deficit etc., so better these patients be subdivided in these categories. Framing universal guidelines all across the world according to subdivisions with appropriate line of care as is being done in various other disorders may help a lot to smoothen improve management and help reduce the cost of therapy and gender bias.
    1. Caoimhe McLoughlin, Ingrid Hoeritzauer, Verónica Cabreira et al. http://dx.doi.org/10.1136/jnnp-2022-330192
    2. Christopher D. Stephen, Vicki Fung, Codrin I. Lungu et al Alberto J. Espay Assessment of Emergency Department and Inpatient Use and Costs in Adult and Pediatric Functional Neur...

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